Rationale

The discovery of the proprotein convertase subtilisin-kexin 9 (PCSK9) in 2003, and its subsequent rapid emergence as a therapeutic target, is today transforming the treatment of cardiovascular disease. Just as the introduction of ‘statins’ in the 1980’s has significantly reduced mortality ...

Biology

Like other proprotein convertases (PCs), PCSK9 undergoes an autocatalytic cleavage of its inhibitory prodomain in the endoplasmic reticulum (ER). This results in a heterodimer of the prosegment and the rest of the mature protein, that is proteolytically inactive and allows the protein ...